Despite the remarkable therapeutic advances achieved with immune checkpoint inhibitors in advanced melanoma, treatment options remain limited for patients with refractory subtypes. This study evaluated a novel combination of DNV3 (anti-LAG-3), toripalimab (anti-PD-1), and chemotherapy (nab-paclitaxel/cisplatin) in 27 Asian patients with unresectable or metastatic melanoma (77.8% 21/27 previously treated with anti-PD-L1 and 22.2% 6/27 treatment-naïve mucosal melanoma; subtypes: 13 mucosal, 6 acral, 5 cutaneous, and 3 of unknown primary origin). The regimen achieved an overall response rate (ORR) of 44.4%, which was further elevated to 54.5% in the subgroup of 11 patients with hepatic metastases. Notably, it also demonstrated substantial efficacy in anti-PD-(L)1-resistant cases, with a 42.9% ORR and a median progression-free survival (PFS) of 7.36 months. Among treatment-naïve mucosal melanoma, the ORR reached 50%. At data cutoff, median overall survival remained unreached in all cohorts. Grade ≥3 treatment-related adverse events initially occurred in 55.6% of participants; subsequent dose modification of nab-paclitaxel (from 260 mg/m2 to 200 mg/m2) improved tolerability, reducing the incidence of grade ≥3 events to 22.2%. Immune-related toxicities (grade 3-4, 22.2%) were clinically manageable. Therefore, the combination of LAG-3/PD-1 blockade and chemotherapy demonstrated promising efficacy, notably in treatment-naïve mucosal melanoma with liver metastases. (Chinese Clinical Trial Registry number, ChiCTR2400079543).
Lin et al. (Sun,) studied this question.